Alcohol induced metabolic alterations - A Case based discussion

Alcohol induced Metabolic Alcohol induced Metabolic AlterationsAlterations

Namrata Chhabra, M.D.

1Namrata Chhabra, M.D.Biochemistry

AlcoholAlcohol

Everything comes at a price

Major pathway of Alcohol metabolism

Products of Alcohol Metabolism

Case details

• A 60 year old man was brought to hospital in a very serious condition.

• The patient complained of o Constant vomiting containing several hundred

mL of dark brown fluid from the previous two days plus

o Several episodes of melaena.

Past History

• Past history of alcoholism, cirrhosis, portal hypertension and a previous episode of bleeding varices was there.

• Sclerotherapy for the varices had been performed several months earlier at another hospital.

Examination

• The patient had jaundice and was in distress, sweaty, clammy and tachypnoeic.

• BP 98/50 mmHg, pulse 120/min. • Heart sounds - systolic murmur.• Peripheries were cold. • Abdomen was soft and non tender. • Signs of chronic liver disease were present (spider

naevi, gynecomastia, and testicular atrophy).

Laboratory Findings

Test Result Reference1) Blood glucose-50mg/dl 65-110 mg/dL2) Lactate 20.3 mmol/L 0.44- 1.8mmol/L3) Urea Nitrogen- 38.6mg/dl 8-25 mg/dL4) Creatinine- 1.24mg/dl 0.7-1.5mg/dL5) Uric acid- 9.8 mg/dL 3-7 mg/dL6) Blood alcohol -550 mg/dl No alcohol

Laboratory findings (contd.)

Test Result Reference7) Na+ 131 mmol/l 136-145 mmol/l.8) Cl- 85 mmol/l 96-106 mmol/l.9) K+ 4.2 mmol/l 3.5-5.5 mmol/L10) HCO3- 14.1 mmol/l 22-28 mmol/l.

Laboratory findings (contd.)

Test Result Reference11) pH 7.21 7.35-7.4512) pCO2 13.8 mmHg 35-45 mm

Hg13) pO2 103 mmHg 80-100 mm Hg

14) Hb 6.2 G/dL 14-18 G/dL 15) W.B.C. count 18 x103/mm3 5-10/ mm3

What is your

diagnosis ?

• The patient has multiple problems• Circulatory failure• GI bleeding on a background of known

Cirrhosis with Portal hypertension• Many other ??

Some Hints???

Some more hints ??

The patient has• Low Blood glucose (Hypoglycemia)• High Lactate• High Uric acid, BUN and creatinine• Electrolyte imbalance• Acid Base imbalance• Low Hb and high W.B.C. Count

• The blood glucose level in this patient is 50 mg/dL, well below the normal range of 65-110 mg/dL.Let’s find out the cause

Hypoglycemia results from an imbalance between demand and supply of glucose

Namrata Chhabra, M.D.Biochemistry

Which of the following conditions best explains the underlying cause of hypoglycemia in this

patient?

A. Impaired activity of Glycogen phosphorylaseB. Impaired activity of Glucose-6-PhosphataseC. Impaired activity of Pyruvate KinaseD. Reduced availability of substrates of

Gluconeogenesis

A) Impaired activity of Glycogen phosphorylase?

B) Impaired activity of Glucose-6-Phosphatase ?

C)Impaired activity of Pyruvate kinase?

D)Reduced availability of substrates of gluconeogenesis

Alcohol metabolism affects availability of substrates of

gluconeogenesis

Correct answer is -D

2) What is the cause of Lactic Acidosis in this patient ?

A. Reversal of reaction catalyzed by lactate dehydrogenase

B. Impaired activity of PDH complexC. Suppressed TCA cycleD. All of the above.

A) Reversal of reaction caused by Lactate dehydrogenase?

Pyruvate is converted to lactate to regenerate NAD +.

B) Impaired activity of PDH complex ?

C) Suppressed activities of TCA cycle enzymes?

TCA cycle

The correct answer is D

Namrata Chhabra, M.D.Biochemistry

• The very low pH indicates a severe acidosis. • The combination of a low pCO2 and low

bicarbonate indicates that it is metabolic acidosis.

Determination of Acid base status

pH H+ P CO2 HCO3-

Normal 7.4 40 mEq/L 40mm Hg 24 mEq/L

Respiratory acidosis

Respiratory Alkalosis

Metabolic acidosis

Metabolic Alkalosis

Cl- mEq/L

mEq/L Na+

mEq/LNa+

mEq/L HCO3-

Cl- mEq/L

A- Normal Ion DistributionB- High anion gap metabolic acidosisC- Normal anion gap acidosis

Anion Gap38Namrata Chhabra, M.D.Biochemistry

Normal or high anion gap metabolic acidosis ?

• The anion gap is 42 indicating the presence of a high anion gap disorder.

• The lactate level of 20.3mmol/l is extremely high and this is responsible for causing high anion gap.

High anion gap acidosis

• High anion gap is also there due to underlying Ketoacidosis.

• Acetyl co A fails to get utilized in TCA cycle, and the excess is channeled towards alternative pathways.

• Gouty arthritis is a common finding in chronic alcoholics

• Gout results from an increased body pool of urate with hyperuricemia.

• It is typically characterized by episodic acute and chronic arthritis, due to deposition of Mono sodium urate crystals in and around joints.

• In the given patient, serum uric acid concentration is higher than normal (9.8 mg/dL).

• What is the cause of Hyperuricemia in this patient?

A. Inhibition of salvage pathway of purine nucleotide biosynthesis

B. Overactive denovo pathway of purine nucleotide biosynthesis

C. Overactive xanthine oxidaseD. Impaired excretion of uric acid

A) Inhibition of salvage pathway?

PRPP Synthetase

B. Overactive denovo pathway of purine nucleotide biosynthesis

PRPP Synthetase

C. Over active Xanthine oxidase ?

PRPP Synthetase

D. Impaired uric acid excretion ?

The correct answer is D-Impaired uric acid excretion

• Additionally hyperuricemia in chronic alcoholism is also due to some other factors

Excess purine nucleotide degradation

High purine content in alcoholic beverages ?

• The higher purine content in some alcoholic beverages such as beer is also an additional factor.

• Urea and creatinine are elevated (renal failure)

• Electrolyte imbalance resulting from acidosis and associated renal failure

• Low Hb - Bleeding and associate nutritional deficiencies

• High W.B.C. Count- Sepsis• Low blood pressure -Circulatory failure

• Cirrhosis and portal hypertension with bleeding varices and

• Sepsis, resulting in shock, • Lactic acidosis, anemia and• Renal failure.

Implications of excess Acetate

Alcohol induced metabolic alterations - A Case based discussion

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